214 resultados para Stiekna, Konrad.


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Der Beitrag diskutiert Möglichkeiten zur Automatisierung von Kundenbeziehungsprozessen im Customer Relationship Management mit Hilfe von Business Rules. Anhand einer CRM-Architektur werden Anwendungsmöglichkeiten erörtert und am Beispiel einer Cross-Selling-Kampagne vertieft. Technische Aspekte werden dabei nicht im Detail betrachtet. Der Schwerpunkt liegt vielmehr in der Diskussion von Automatisierungs- und Integrationspotenzialen durch den Einsatz von Business Rules, wie sie in zunehmend individualisierten Kundenbeziehungen in Massenmärkten gegeben sind.

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Many viruses significantly impact human and animal health. Understanding the population dynamics of these viruses and their hosts can provide important insights for epidemiology and virus evolution. Puumala virus (PUUV) is a European hantavirus that may cause regional outbreaks of hemorrhagic fever with renal syndrome in humans. Here, we analyzed the spatiotemporal dynamics of PUUV circulating in local populations of its rodent reservoir host, the bank vole (Myodes glareolus) during eight years. Phylogenetic and population genetic analyses of all three genome segments of PUUV showed strong geographical structuring at a very local scale. There was a high temporal turnover of virus strains in the local bank vole populations, but several virus strains persisted through multiple years. Phylodynamic analyses showed no significant changes in the local effective population sizes of PUUV, although vole numbers and virus prevalence fluctuated widely. Microsatellite data demonstrated also a temporally persisting subdivision between local vole populations, but these groups did not correspond to the subdivision in the virus strains. We conclude that restricted transmission between vole populations and genetic drift play important roles in shaping the genetic structure and temporal dynamics of PUUV in its natural host which has several implications for zoonotic risks of the human population.

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The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 European participants. The aim of the consortium is to promote and sustain collaboration and sharing of data and knowledge in the field of ophthalmic epidemiology in Europe, with particular focus on the harmonization of methods for future research, estimation and projection of frequency and impact of visual outcomes in European populations (including temporal trends and European subregions), identification of risk factors and pathways for eye diseases (lifestyle, vascular and metabolic factors, genetics, epigenetics and biomarkers) and development and validation of prediction models for eye diseases. Coordinating these existing data will allow a detailed study of the risk factors and consequences of eye diseases and visual impairment, including study of international geographical variation which is not possible in individual studies. It is expected that collaborative work on these existing data will provide additional knowledge, despite the fact that the risk factors and the methods for collecting them differ somewhat among the participating studies. Most studies also include biobanks of various biological samples, which will enable identification of biomarkers to detect and predict occurrence and progression of eye diseases. This article outlines the rationale of the consortium, its design and presents a summary of the methodology.

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Proton therapy is a high precision technique in cancer radiation therapy which allows irradiating the tumor with minimal damage to the surrounding healthy tissues. Pencil beam scanning is the most advanced dose distribution technique and it is based on a variable energy beam of a few millimeters FWHM which is moved to cover the target volume. Due to spurious effects of the accelerator, of dose distribution system and to the unavoidable scattering inside the patient's body, the pencil beam is surrounded by a halo that produces a peripheral dose. To assess this issue, nuclear emulsion films interleaved with tissue equivalent material were used for the first time to characterize the beam in the halo region and to experimentally evaluate the corresponding dose. The high-precision tracking performance of the emulsion films allowed studying the angular distribution of the protons in the halo. Measurements with this technique were performed on the clinical beam of the Gantry1 at the Paul Scherrer Institute. Proton tracks were identified in the emulsion films and the track density was studied at several depths. The corresponding dose was assessed by Monte Carlo simulations and the dose profile was obtained as a function of the distance from the center of the beam spot.

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Radioactivity induced by a 15-MeV proton beam extracted into air was studied at the beam transport line of the 18-MeV cyclotron at the Bern University Hospital (Inselspital). The produced radioactivity was calculated and measured by means of proportional counters located at the main exhaust of the laboratory. These devices were designed for precise assessment of air contamination for radiation protection purposes. The main produced isotopes were 11C, 13N and 14O. Both measurements and calculations correspond to two different irradiation conditions. In the former, protons were allowed to travel for their full range in air. In the latter, they were stopped at the distance of 1.5 m by a beam dump. Radioactivity was measured continuously in the exhausted air starting from 2 min after the end of irradiation. For this reason, the short-lived 14O isotope gave a negligible contribution to the measured activity. Good agreement was found between the measurements and the calculations within the estimated uncertainties. Currents in the range of 120–370 nA were extracted in air for 10–30 s producing activities of 9–22 MBq of 11C and 13N. The total activities for 11C and 13N per beam current and irradiation time for the former and the latter irradiation conditions were measured to be (3.60 ± 0.48) × 10−3 MBq (nA s)−1 and (2.89 ± 0.37) × 10−3 MBq (nA s)−1, respectively.

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A medical cyclotron accelerating H- ions to 18 MeV is in operation at the Bern University Hospital (Inselspital). It is the commercial IBA 18/18 cyclotron equipped with a specifically conceived 6 m long external beam line ending in a separate bunker. This feature is unique for a hospital-based facility and makes it possible to conduct routine radioisotope production for PET diagnostics in parallel with multidisciplinary research activities, among which are novel particle detectors, radiation biophysics, radioprotection, radiochemistry and radiopharmacy developments. Several of these activities, such as radiobiology experiments for example, require low current beams down to the pA range, while medical cyclotrons are designed for high current operation above 10 μA. In this paper, we present the first results on the low current performance of a PET medical cyclotron obtained by ion source, radio-frequency and main coil tuning. With this method, stable beam currents down to (1.5+/- 0.5 ) pA were obtained and measured with a high-sensitivity Faraday cup located at the end of the beam transport line.

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The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen’s d effect sizes: −0.10 to −0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: −0.26 to −0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

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BACKGROUND The metacestode of the tapeworm Echinococcus multilocularis is the causative agent of alveolar echinococcosis, a lethal zoonosis. Infections are initiated through establishment of parasite larvae within the intermediate host's liver, where high concentrations of insulin are present, followed by tumour-like growth of the metacestode in host organs. The molecular mechanisms determining the organ tropism of E. multilocularis or the influences of host hormones on parasite proliferation are poorly understood. RESULTS Using in vitro cultivation systems for parasite larvae we show that physiological concentrations (10 nM) of human insulin significantly stimulate the formation of metacestode larvae from parasite stem cells and promote asexual growth of the metacestode. Addition of human insulin to parasite larvae led to increased glucose uptake and enhanced phosphorylation of Echinococcus insulin signalling components, including an insulin receptor-like kinase, EmIR1, for which we demonstrate predominant expression in the parasite's glycogen storage cells. We also characterized a second insulin receptor family member, EmIR2, and demonstrated interaction of its ligand binding domain with human insulin in the yeast two-hybrid system. Addition of an insulin receptor inhibitor resulted in metacestode killing, prevented metacestode development from parasite stem cells, and impaired the activation of insulin signalling pathways through host insulin. CONCLUSIONS Our data indicate that host insulin acts as a stimulant for parasite development within the host liver and that E. multilocularis senses the host hormone through an evolutionarily conserved insulin signalling pathway. Hormonal host-parasite cross-communication, facilitated by the relatively close phylogenetic relationship between E. multilocularis and its mammalian hosts, thus appears to be important in the pathology of alveolar echinococcosis. This contributes to a closer understanding of organ tropism and parasite persistence in larval cestode infections. Furthermore, our data show that Echinococcus insulin signalling pathways are promising targets for the development of novel drugs.

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A detector based on doped silica and optical fibers was developed to monitor the profile of particle accelerator beams of intensity ranging from 1 pA to tens of µA. Scintillation light produced in a fiber moving across the beam is measured, giving information on its position, shape and intensity. The detector was tested with a continuous proton beam at the 18 MeV Bern medical cyclotron used for radioisotope production and multi-disciplinary research. For currents from 1 pA to 20 µA, Ce3+ and Sb3+ doped silica fibers were used as sensors. Read out systems based on photodiodes, photomultipliers and solid state photomultipliers were employed. Profiles down to the pA range were measured with this method for the first time. For currents ranging from 1 pA to 3 µA, the integral of the profile was found to be linear with respect to the beam current, which can be measured by this detector with an accuracy of ∼1%. The profile was determined with a spatial resolution of 0.25 mm. For currents ranging from 5 µA to 20 µA, thermal effects affect light yield and transmission, causing distortions of the profile and limitations in monitoring capabilities. For currents higher than ∼1 µA, non doped optical fibers for both producing and transporting scintillation light were also successfully employed.